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1.
Genet Epidemiol ; 47(1): 105-118, 2023 02.
Article in English | MEDLINE | ID: mdl-36352773

ABSTRACT

The minor allele of rs373863828, a missense variant in CREB3 Regulatory Factor, is associated with several cardiometabolic phenotypes in Polynesian peoples. To better understand the variant, we tested the association of rs373863828 with a panel of correlated phenotypes (body mass index [BMI], weight, height, HDL cholesterol, triglycerides, and total cholesterol) using multivariate Bayesian association and network analyses in a Samoa cohort (n = 1632), Aotearoa New Zealand cohort (n = 1419), and combined cohort (n = 2976). An expanded set of phenotypes (adding estimated fat and fat-free mass, abdominal circumference, hip circumference, and abdominal-hip ratio) was tested in the Samoa cohort (n = 1496). In the Samoa cohort, we observed significant associations (log10 Bayes Factor [BF] ≥ 5.0) between rs373863828 and the overall phenotype panel (8.81), weight (8.30), and BMI (6.42). In the Aotearoa New Zealand cohort, we observed suggestive associations (1.5 < log10 BF < 5) between rs373863828 and the overall phenotype panel (4.60), weight (3.27), and BMI (1.80). In the combined cohort, we observed concordant signals with larger log10 BFs. In the Samoa-specific expanded phenotype analyses, we also observed significant associations between rs373863828 and fat mass (5.65), abdominal circumference (5.34), and hip circumference (5.09). Bayesian networks provided evidence for a direct association of rs373863828 with weight and indirect associations with height and BMI.


Subject(s)
Adiposity , Pacific Island People , Tumor Suppressor Proteins , Humans , Bayes Theorem , Body Mass Index , Multivariate Analysis , Obesity/genetics , Tumor Suppressor Proteins/genetics , Mutation, Missense
2.
J Hum Genet ; 68(7): 463-468, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36864286

ABSTRACT

The fat mass and obesity associated (FTO) locus consistently associates with higher body mass index (BMI) across diverse ancestral groups. However, previous small studies of people of Polynesian ancestries have failed to replicate the association. In this study, we used Bayesian meta-analysis to test rs9939609, the most replicated FTO variant, for association with BMI with a large sample (n = 6095) of Aotearoa New Zealanders of Polynesian (Maori and Pacific) ancestry and of Samoan people living in the Independent State of Samoa and in American Samoa. We did not observe statistically significant association within each separate Polynesian subgroup. Bayesian meta-analysis of the Aotearoa New Zealand Polynesian and Samoan samples resulted in a posterior mean effect size estimate of +0.21 kg/m2, with a 95% credible interval [+0.03 kg/m2, +0.39 kg/m2]. While the Bayes Factor (BF) of 0.77 weakly favors the null, the BF = 1.4 Bayesian support interval is [+0.04, +0.20]. These results suggest that rs9939609 in FTO may have a similar effect on mean BMI in people of Polynesian ancestries as previously observed in other ancestral groups.


Subject(s)
Body Mass Index , Maori People , Pacific Island People , Humans , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Bayes Theorem , Genetic Predisposition to Disease , Maori People/genetics , New Zealand , Pacific Island People/genetics , Polymorphism, Single Nucleotide
3.
Proc Natl Acad Sci U S A ; 117(17): 9458-9465, 2020 04 28.
Article in English | MEDLINE | ID: mdl-32291332

ABSTRACT

Archaeological studies estimate the initial settlement of Samoa at 2,750 to 2,880 y ago and identify only limited settlement and human modification to the landscape until about 1,000 to 1,500 y ago. At this point, a complex history of migration is thought to have begun with the arrival of people sharing ancestry with Near Oceanic groups (i.e., Austronesian-speaking and Papuan-speaking groups), and was then followed by the arrival of non-Oceanic groups during European colonialism. However, the specifics of this peopling are not entirely clear from the archaeological and anthropological records, and is therefore a focus of continued debate. To shed additional light on the Samoan population history that this peopling reflects, we employ a population genetic approach to analyze 1,197 Samoan high-coverage whole genomes. We identify population splits between the major Samoan islands and detect asymmetrical gene flow to the capital city. We also find an extreme bottleneck until about 1,000 y ago, which is followed by distinct expansions across the islands and subsequent bottlenecks consistent with European colonization. These results provide for an increased understanding of Samoan population history and the dynamics that inform it, and also demonstrate how rapid demographic processes can shape modern genomes.


Subject(s)
Biological Evolution , Native Hawaiian or Other Pacific Islander/genetics , Archaeology , Demography , Humans , Samoa , Time Factors
4.
Environ Res ; 207: 112220, 2022 05 01.
Article in English | MEDLINE | ID: mdl-34656632

ABSTRACT

BACKGROUND: Few studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy. METHODS: We analyzed data from 346 women with a singleton live birth in the HOME Study, a prospective birth cohort in Cincinnati, Ohio, USA. We quantified four OPE metabolites in maternal spot urine samples collected at 16 and 26 weeks pregnancy, standardized by specific gravity. We calculated intraclass correlation coefficients (ICCs). We extracted the first two recorded BP measurements (<20 weeks), the two highest recorded BP measurements (≥20 weeks), and diagnoses of hypertensive disorders of pregnancy (HDP) via chart review. Women with two BP measurements ≥140/90 mmHg or HDP noted in the chart at ≥20 weeks pregnancy were defined as HDP cases. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations as continuous variables or in tertiles with maternal BP and HDP. RESULTS: ICCs of OPEs were 0.17-0.45. Diphenyl phosphate (DPHP) had the highest geometric mean concentration among OPE metabolites. Increasing the average bis(2-chloroethyl) phosphate (BCEP) concentrations were positively associated with two highest recorded DBP ≥20 weeks pregnancy. Compared with women in the 1st DPHP tertile, women in the 3rd tertile at 16 weeks pregnancy had 1.72 mmHg (95% CI: -0.01, 3.46) higher DBP <20 weeks pregnancy, and women in the 3rd tertile of the average DPHP concentrations had 2.25 mmHg (95% CI: 0.25, 4.25) higher DBP ≥20 weeks pregnancy. 33 women (9.5%) were identified with HDP. Di-n-butyl phosphate (DNBP) concentrations at 16 weeks were positively associated with HDP, with borderline significance (RR = 2.98, 95% CI 0.97-9.15). Other OPE metabolites were not significantly associated with HDP. CONCLUSION: Maternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance.


Subject(s)
Esters , Flame Retardants , Blood Pressure , Female , Gestational Age , Humans , Organophosphates/urine , Pregnancy , Prospective Studies
5.
Nutr Metab Cardiovasc Dis ; 32(2): 346-354, 2022 02.
Article in English | MEDLINE | ID: mdl-34953632

ABSTRACT

BACKGROUND AND AIMS: Metabolic syndrome (MetS) affects ∼10% of adolescents and is associated with cardiometabolic disease risk. The most prevalent MetS component is abdominal obesity. Healthy diet and physical activity (PA) are inversely associated with abdominal obesity and may reduce MetS risk in youth. Our aim was to examine associations of diet, activity, and abdominal obesity with MetS z-score (MetS-z). METHODS AND RESULTS: An analysis of National Health and Nutrition Examination Survey (NHANES) 2011-2016 data in adolescents was performed. Healthy Eating Index (HEI)- 2015 scores were calculated for diet quality, PA habits were used to determine alignment with national guidelines, and abdominal obesity was assessed by sagittal abdominal diameter (SAD). MetS-z represented severity or potential risk for MetS. Multivariable regression evaluated the relationships of HEI, SAD and PA with MetS-z. Among 1214 black and white adolescents, SAD was significantly associated with MetS-z [ß (95% CI) = 0.17 (0.16, 0.19); P <0.0001] while HEI-2015 components showed associations with MetS-z overall (HEI total, dairy, and sodium scores), and by sex (total, refined grains, dairy for males; added sugar, protein, whole grains for females). Mean HEI-2015 score was 47.4/100 (51.6 using the population-ratio method), and the proportion of adolescents meeting national PA guidelines was 37.6%, yet PA was not a significant predictor of MetS-z. CONCLUSIONS: US adolescents have poor diet quality and fewer than half meet PA guidelines. Strategies for preventing MetS and related conditions in adolescence should focus on weight management - specifically, abdominal fat reduction - with individualized diet counseling.


Subject(s)
Metabolic Syndrome , Obesity, Abdominal , Adolescent , Diet/adverse effects , Exercise , Female , Humans , Male , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Metabolic Syndrome/prevention & control , Nutrition Surveys , Obesity, Abdominal/diagnosis , Obesity, Abdominal/epidemiology
6.
J Hum Genet ; 66(2): 111-121, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32759990

ABSTRACT

The current understanding of the genetic architecture of lipids has largely come from genome-wide association studies (GWAS). To date, few GWAS have examined the genetic architecture of lipids in Polynesians, and none have in Samoans, whose unique population history, including many population bottlenecks, may provide insight into the biological foundations of variation in lipid levels. Here we performed a GWAS of four fasting serum lipid levels: total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) in a sample of 2849 Samoans, with validation genotyping for associations in a replication cohort comprising 1798 Samoans and American Samoans. We identified multiple genome-wide significant associations (P < 5 × 10-8) previously seen in other populations-APOA1 with TG, CETP with HDL, and APOE with TC and LDL-and several suggestive associations (P < 1 × 10-5), including an association of variants downstream of MGAT1 and RAB21 with HDL. However, we observed different association signals for variants near APOE than what has been previously reported in non-Polynesian populations. The association with several known lipid loci combined with the newly identified associations with variants near MGAT1 and RAB21 suggest that while some of the genetic architecture of lipids is shared between Samoans and other populations, part of the genetic architecture may be Polynesian-specific.


Subject(s)
Genetic Markers , Genome-Wide Association Study , Lipid Metabolism/genetics , Lipids/blood , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Adult , Apolipoprotein A-I/genetics , Apolipoproteins E/genetics , Cholesterol Ester Transfer Proteins/genetics , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cohort Studies , Fasting , Female , Humans , Male , Middle Aged , Samoa , Triglycerides/blood
7.
Am J Hum Biol ; 32(6): e23414, 2020 11.
Article in English | MEDLINE | ID: mdl-32190945

ABSTRACT

OBJECTIVES: Studies have demonstrated that rs373863828, a missense variant in CREBRF, is associated with a number of anthropometric traits including body mass index (BMI), obesity, percent body fat, hip circumference, and abdominal circumference. Given the biological relationship between height and adiposity, we hypothesized that the effect of this variant on BMI might be due in part to an association of this variant with height. METHODS: We tested the hypothesis that minor allele of rs373863828 is associated with height in a Samoan population in two adult cohorts and in a separate cohort of children (age 5-18 years old) using linear mixed modeling. RESULTS: We found evidence of a strong relationship between rs373863828 and greater mean height in Samoan adults (0.77 cm greater average height for each copy of the minor allele) with the same direction of effect in Samoan children. CONCLUSIONS: These results suggest that the missense variant rs373863828 in CREBRF, first identified through an association with larger BMI, may be related to an underlying biological mechanism affecting overall body size including stature.


Subject(s)
Body Height/genetics , Mutation, Missense/genetics , Tumor Suppressor Proteins/genetics , Adolescent , Adult , American Samoa , Child , Child, Preschool , Cohort Studies , Female , Humans , Male , Middle Aged , Samoa
8.
Diabetologia ; 61(7): 1603-1613, 2018 07.
Article in English | MEDLINE | ID: mdl-29721634

ABSTRACT

AIMS/HYPOTHESIS: The A (minor) allele of CREBRF rs373863828 has been associated with increased BMI and reduced risk of type 2 diabetes in the Samoan populations of Samoa and American Samoa. Our aim was to test rs373863828 for associations with BMI and the odds of type 2 diabetes, gout and chronic kidney disease (CKD) in Maori and Pacific (Polynesian) people living in Aotearoa/New Zealand. METHODS: Linear and logistic regression models were used to analyse the association of the A allele of CREBRF rs373863828 with BMI, log-transformed BMI, waist circumference, type 2 diabetes, gout and CKD in 2286 adults. The primary analyses were adjusted for age, sex, the first four genome-wide principal components and (where appropriate) BMI, waist circumference and type 2 diabetes. The primary analysis was conducted in ancestrally defined groups and association effects were combined using meta-analysis. RESULTS: For the A allele of rs373863828, the effect size was 0.038 (95% CI 0.022, 0.055, p = 4.8 × 10-6) for log-transformed BMI, with OR 0.59 (95% CI 0.47, 0.73, p = 1.9 × 10-6) for type 2 diabetes. There was no evidence for an association of genotype with variance in BMI (p = 0.13), and nor was there evidence for associations with serum urate (ß = 0.012 mmol/l, pcorrected = 0.10), gout (OR 1.00, p = 0.98) or CKD (OR 0.91, p = 0.59). CONCLUSIONS/INTERPRETATION: Our results in New Zealand Polynesian adults replicate, with very similar effect sizes, the association of the A allele of rs373863828 with higher BMI but lower odds of type 2 diabetes among Samoan adults living in Samoa and American Samoa.


Subject(s)
Body Mass Index , Diabetes Mellitus, Type 2/prevention & control , Native Hawaiian or Other Pacific Islander/genetics , Obesity/genetics , Polymorphism, Single Nucleotide , Tumor Suppressor Proteins/genetics , Adult , Aged , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/genetics , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , New Zealand/epidemiology , Obesity/diagnosis , Obesity/ethnology , Phenotype , Polynesia/ethnology , Protective Factors , Risk Factors
9.
Am J Hum Genet ; 94(4): 511-21, 2014 Apr 03.
Article in English | MEDLINE | ID: mdl-24656865

ABSTRACT

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.


Subject(s)
Cerebral Hemorrhage/genetics , Chromosomes, Human, Pair 1 , Genetic Predisposition to Disease , Genome-Wide Association Study , Case-Control Studies , Humans , Quantitative Trait Loci
10.
Am J Hum Biol ; 29(3)2017 May 06.
Article in English | MEDLINE | ID: mdl-28121389

ABSTRACT

OBJECTIVES: Positioned at the nexus of India, China, and Southeast Asia, Northeast India is presumed to have served as a channel for land-based human migration since the Upper Pleistocene. Assam is the largest state in the Northeast. We characterized the genetic background of three populations and examined the ways in which their population histories and cultural practices have influenced levels of intrasample and intersample variation. METHODS: We examined sequence data from the mtDNA hypervariable control region and selected diagnostic mutations from the coding region in 128 individuals from three ethnic groups currently living in Assam: two Scheduled tribes (Sonowal Kachari and Rabha), and the non-Scheduled Tai Ahom. RESULTS: The populations of Assam sampled here express mtDNA lineages indicative of South Asian, Southeast Asian, and East Asian ancestry. We discovered two completely novel haplogroups in Assam that accounted for 6.2% of the lineages in our sample. We also identified a new subhaplogroup of M9a that is prevalent in the Sonowal Kachari of Assam (19.1%), but not present in neighboring Arunachal Pradesh, indicating substantial regional population structuring. Employing a large comparative dataset into a series of multidimensional scaling (MDS) analyses, we saw the Rabha cluster with populations sampled from Yunnan Province, indicating that the historical matrilineality of the Rabha has maintained lineages from Southern China. CONCLUSION: Assam has undergone multiple colonization events in the time since the initial peopling event, with populations from Southern China and Southeast Asia having the greatest influence on maternal lineages in the region.


Subject(s)
Genetic Variation , Haplotypes , DNA, Mitochondrial/genetics , Ethnicity/genetics , Evolution, Molecular , Humans , India
11.
Stroke ; 46(8): 2299-301, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26111891

ABSTRACT

BACKGROUND AND PURPOSE: Intracerebral hemorrhage has a substantial genetic component. We performed a preliminary search for rare coding variants associated with intracerebral hemorrhage. METHODS: A total of 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc, San Diego, CA). Meta-analyses of single-variant and gene-based association were computed. RESULTS: No rare coding variants were associated with intracerebral hemorrhage. Three common variants on chromosome 19q13 at an established susceptibility locus, encompassing TOMM40, APOE, and APOC1, met genome-wide significance (P<5e-08). After adjusting for the APOE epsilon alleles, this locus was no longer convincingly associated with intracerebral hemorrhage. No gene reached genome-wide significance level in gene-based association testing. CONCLUSIONS: Although no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci; large sample sizes are required for sufficient power except for loci with large effects.


Subject(s)
Cerebral Hemorrhage/genetics , Genetic Predisposition to Disease/genetics , Genetic Variation/genetics , Genome-Wide Association Study/methods , Aged , Aged, 80 and over , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/epidemiology , Female , Genetic Predisposition to Disease/epidemiology , Humans , Male , Middle Aged , Risk Factors
12.
Cerebrovasc Dis ; 39(2): 82-6, 2015.
Article in English | MEDLINE | ID: mdl-25571891

ABSTRACT

BACKGROUND AND PURPOSE: Very few cases of intracranial aneurysms (IAs) in twins have been reported. Previous work has suggested that vulnerability to IA formation is heritable. Twin studies provide an opportunity to evaluate the impact of genetics on IA characteristics, including IA location. We therefore sought to examine IA location concordance, multiplicity, and rupture status within affected twin-pairs. METHODS: The Familial Intracranial Aneurysm study was a multicenter study whose goal was to identify genetic and other risk factors for formation and rupture of IAs. The study required at least three affected family members or an affected sibling pair for inclusion. Subjects with fusiform aneurysms, an IA associated with an AVM, or a family history of conditions known to predispose to IA formation, such as polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome were excluded. Twin-pairs were identified by birth date and were classified as monozygotic (MZ) or dizygotic (DZ) through DNA marker genotypes. In addition to zygosity, we evaluated twin-pairs by smoking status, major arterial territory of IAs, and rupture status. Location concordance was defined as the presence of an IA in the same arterial distribution (ICA, MCA, ACA, and vertebrobasilar), irrespective of laterality, in both members of a twin-pair. The Fisher exact test was used for comparisons between MZ and DZ twin-pairs. RESULTS: A total of 16 affected twin-pairs were identified. Location concordance was observed in 8 of 11 MZ twin-pairs but in only 1 of 5 DZ twin-pairs (p = 0.08). Three MZ subjects had unknown IA locations and comprised the three instances of MZ discordance. Six of the 11 MZ twin-pairs and none of the 5 DZ twin-pairs had IAs in the ICA distribution (p = 0.03). Multiple IAs were observed in 11 of 22 MZ and 5 of 10 DZ twin-pairs. Thirteen (13) of the 32 subjects had an IA rupture, including 10 of 22 MZ twins. CONCLUSIONS: We found that arterial location concordance was greater in MZ than DZ twins, which suggests a genetic influence upon aneurysm location. The 16 twin-pairs in the present study are nearly the total of affected twin-pairs that have been reported in the literature to date. Further studies are needed to determine the impact of genetics in the formation and rupture of IAs.


Subject(s)
Aneurysm, Ruptured/genetics , Intracranial Aneurysm/genetics , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Adult , Aged , Female , Humans , Intracranial Aneurysm/pathology , Magnetic Resonance Angiography , Male , Middle Aged , Rupture, Spontaneous , Smoking , Young Adult
13.
Coll Antropol ; 39(2): 401-9, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26753457

ABSTRACT

The objective of the study was to examine the association between fish and shellfish intake and diabetes in an island population, and the design of the study was Cross-sectional. Two independent population-based field surveys were conducted in Hvar Island of the eastern Adriatic coast of Croatia in May 2007 and May 2008, with a total of 1,379 adult participants. In multivariable logistic regression models, total fish intake was positively associated with diabetes prevalence in the total population (OR(Q4 vs. Q1) = 1.64; 95% CI = 1.01-2.66; p-trend = 0.09). Oily fish intake also exhibited a positive association with diabetes prevalence in the total population (OR(Q4 vs. Q1) = 2.22; 95% CI = 1.35-3.64; p-trend = 0.01) and in analyses stratified by body mass index, males and those with a high waist circumference. The study suggests an association between oily fish intake and diabetes in the population of the Hvar Island in Croatia. Longitudinal studies incorporating measures of persistent organic pollutants and local cooking practices are warranted to identify factors in fatty fish that may influence the development or persistence of diabetes.


Subject(s)
Diabetes Mellitus/etiology , Diet , Seafood , Shellfish , Adult , Aged , Croatia , Female , Humans , Male , Middle Aged , Risk Factors
14.
Am J Hum Biol ; 26(4): 491-501, 2014.
Article in English | MEDLINE | ID: mdl-24799123

ABSTRACT

OBJECTIVE: To describe the prevalence of obesity-related noncommunicable diseases (NCDs) and associated risk factors in a sample of Samoan adults studied in 2010 as part of a genome-wide assocation study (GWAS) for obesity related traits. METHODS: Anthropometric and biochemical data collected from n = 3,475 participants (n = 1,437 male; n = 2,038 female) aged 24.5 to <65 years were used to describe the prevalence of obesity, diabetes, hypertension, and dyslipidemia within the study sample. One way analysis of variance, χ(2) tests, and binary logistic regression were used to identify differences in disease and risk factor prevalence by 10-year age group, gender, or by census region of residence. RESULTS: Obesity was highly prevalent among the study sample; 64.6% of females and 41.2% of males were obese according to Polynesian cutoffs (BMI ≥ 32 kg/m(2) ). Females were less likely than males to have hypertension (31.7% vs. 36.7%) but equally likely to have diabetes (17.8% vs. 16.4%). With the exception of obesity and low HDL-cholesterol in females only, there were significant differences in the prevalence of all NCDs and associated risk factors by age group, with the oldest age group (55 to <65 years) most affected. In both sexes, residents of the Apia Urban Area were at significantly greater risk of obesity, diabetes, low HDL-cholesterol, and high triglycerides than residents of the more rural Savaii region. CONCLUSIONS: The phenotypic characteristics of this sample provide evidence of a continuation of previously reported temporal trends toward obesity and its associated disorders. Attention must be paid to the critical NCD situation in Samoa.


Subject(s)
Genetic Variation , Genome-Wide Association Study , Hypertension/epidemiology , Metabolic Diseases/epidemiology , Obesity/epidemiology , Adiposity , Adult , Environment , Female , Humans , Hypertension/etiology , Independent State of Samoa/epidemiology , Male , Metabolic Diseases/etiology , Middle Aged , Obesity/etiology , Prevalence , Risk Factors , Socioeconomic Factors , Young Adult
15.
Stroke ; 44(1): 38-42, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23204049

ABSTRACT

BACKGROUND AND PURPOSE: Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. METHODS: We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family's proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. RESULTS: There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04-2.27]; P=0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22-3.22]; P=0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05-8.24], P=0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34-2.46]; P<0.001). CONCLUSIONS: In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.


Subject(s)
Family , Genetic Predisposition to Disease/genetics , Intracranial Aneurysm/genetics , Intracranial Aneurysm/pathology , Quantitative Trait, Heritable , Adult , Female , Humans , Male , Middle Aged , Pedigree
16.
Stroke ; 44(11): 3013-7, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24008570

ABSTRACT

BACKGROUND AND PURPOSE: Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH). Although statins have been associated with an increased risk of ICH, meta-analyses have not consistently shown a statin-induced risk of ICH. Here, we test whether hypercholesterolemia (HC) and ApoE polymorphisms affect the risk of ICH by statin use. METHODS: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) study is a prospective, demographically matched case-control study of ICH. A similar study of ICH, Genetic Risks for Medication-Related Hemorrhagic Stroke (GOCHA), was used as a replication cohort. Subjects were classified as normocholesterolemia, HC without statin use, and HC with statin use. Statistical comparisons were performed using Fisher exact test, χ2 tests, and the Breslow-Day test. RESULTS: The discovery cohort consisted of 558 ICH cases and 1444 controls, and the replication cohort consisted of 1020 ICH cases and 382 controls. The association of lower risk for HC was not attenuated by statin use. Statin use was observed to confer a higher risk for lobar ICH in those carrying ApoE4/E4 and ApoE2/E4 genotypes in both discovery and replication cohorts, and a test for interaction showed a trend towards significance (P=0.11 for statin and ApoE4/E4). CONCLUSIONS: Statin use does not seem to attenuate the association of HC with decreased risk for nonlobar ICH. Our data support a gene-by-drug effect for lobar ICH, but larger sample sizes are needed to confirm the association before any clinical change is warranted. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00930280.


Subject(s)
Apolipoproteins E/metabolism , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/genetics , Aged , Apolipoproteins E/genetics , Case-Control Studies , Cerebral Hemorrhage/chemically induced , Female , Genotype , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Male , Middle Aged , Prospective Studies , Risk Factors
18.
Coll Antropol ; 37(3): 745-53, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24308211

ABSTRACT

The study deals with the connection between metabolic syndrome (MS) and smoking habits of 1602 males and 828 females aged 18-97 years from the island of Hvar, Croatia. The age-adjusted prevalence of MS was higher in males (18.1-31.2%) than females (9.7-24.2%) by all five criteria that were defined, except the one by AHA/NHLBI. The overall prevalence of MS reached 12.9% by WHO using body mass index (BMI), 13.1% by EGIR, 14.5% by WHO using waist to hip ratio (WHR), 18.2% by NCEP/ATP III, 18.9% by AHA/NHLBI, and 26.7% by IDF criteria. The prevalence of smoking habits was similar in males (24.7%) and females (23.8%). The frequency of mild, moderate and heavy smoking was higher in males than females, 35.8:26.6%, 31.0:27.0%, and 35.9:7.7%, respectively. Age and sex had significant influence on BMI and WHR, both being highest in male former smokers (28.15 kg/m2 and 0.973, respectively) and in female non-smokers (27.18 kg/m2 and 0.869, respectively). The appearance of arterial hypertension (HTN) differed according to frequency of smoking; males had higher prevalence than females using WHO and EGIR criteria of blood pressure > or = 140/90 mmHg, even after age adjustment. In males and females respectively, systolic HTN in non-smokers was 20.7:15.1%, in former smokers 17.9:15.2% and in current smokers 16.9:13.0%; diastolic HTN in non-smokers was 19.8:12.7%, in former smokers 22.4:10.5%, and in current smokers 11.3:9.1%. By NCEP, AHA, IDF criteria of blood pressure > or = 130/85 mmHg, arterial HTN was also more prevalent in males than females; systolic HTN in non-smokers being 31.4:19.8%, in former smokers 29.9:12.7%, and in current smokers 25.4:11.1%; and diastolic HTN in non-smokers was 20.5:11.5%, in former smokers 24.8:11.3%, and in current smokers 14.7:9.4%. According to AHA/NHLBI and IDF criteria of high plasma glucose as > or = 5.6 mmoL/L, both males and females in all the three categories of smokers had glucose levels above the normal range (5.80-6.31 mmol/L in males and 5.80-5.91 mmol/L in females), except female current smokers (5.51 mmol/L). By WHO, EGIR and NCEP/ATP III criteria of high plasma glucose as > or = 6.1 mmol/L, only male non-smokers (6.31 mmol/L) and former smokers (6.24 mmol/L) had elevated levels. Considering normal HDL-cholesterol as > 1.0 mmol/L in males and > 1.2 mmol/L in females, both males and females in all the three smoker's categories had HDL within normal range; females having higher HDL levels (1.52 mmol/L) than males (1.30 mmol/L). Considering normal value for triglycerides as < 1.7 mmol/L, male former smokers (1.76 mmol/L) and current smokers (1.81 mmol/L) had higher levels; and as a whole group triglycerides were higher in males than females, 1.66:1.37 mmol/L respectively. The prevalence of MS differed between males and females using various MS criteria. Both males and females had the highest prevalence of MS by IDF criteria; male former smokers 60.5%, female non-smokers 51.4%, male non-smokers 53.8%, female former smokers 38.2%, and lowest in both male and female current smokers 39.8 and 33.0% respectively. In males, the lowest prevalence of MS was observed in non-smokers by AHA criteria (30.5%), in former smokers by WHO criteria (35.7%), and in current smokers using EGIR criteria (18.1%). Females in all the three smoker's categories had the lowest prevalence of MS using EGIR and WHO criteria. MS were less prevalent in current smokers than in non-smokers and former smokers.


Subject(s)
Hyperglycemia/blood , Hyperglycemia/epidemiology , Hyperlipidemias/blood , Hyperlipidemias/epidemiology , Smoking/epidemiology , Smoking/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Croatia/epidemiology , Female , Humans , Islands/epidemiology , Male , Middle Aged , Prevalence , Young Adult
19.
Coll Antropol ; 37(2): 335-42, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23940972

ABSTRACT

Adriatic islanders have a high prevalence of metabolic syndrome (MetS) although they have traditionally practiced an active lifestyle and adhered to a Mediterranean diet. We performed a cross-sectional study to identify dietary patterns in a sample of 1442 adults from the island of Hvar, and determined whether MetS and its components: waist-circumference, serum triglycerides, fasting plasma glucose, HDL-cholesterol, and blood pressure, were related to an altered pattern of the traditional Mediterranean diet. Dietary intake was assessed by a food frequency questionnaire. MetS was defined using the International Diabetes Federation criteria. Our study showed that dietary patterns in this population have diversified from the traditional diet. Principal component analysis identified three major patterns. The meat, alcohol, and fish pattern (MAFp), sweets, grains, and fats pattern (SGFp), and an olive-oil, vegetables, and fruits pattern (OVFp) explained 30.6% of total dietary variance. The MAFp associated significantly with MetS (p = 0.027) and high plasma glucose (p = 0.006).


Subject(s)
Diet, Mediterranean/ethnology , Feeding Behavior/ethnology , Metabolic Syndrome/ethnology , Metabolic Syndrome/prevention & control , Adult , Aged , Aged, 80 and over , Croatia , Cross-Sectional Studies , Female , Humans , Islands , Male , Middle Aged , Prevalence , Young Adult
20.
Surg Obes Relat Dis ; 19(4): 350-355, 2023 04.
Article in English | MEDLINE | ID: mdl-36414523

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) affects ∼10% of U.S. adolescents. Abdominal obesity is the most prevalent component and may indicate MetS risk in adolescents undergoing weight loss surgery. OBJECTIVES: Assess MetS risk/severity and its association with abdominal obesity (measured by sagittal abdominal diameter, SAD) before and after weight loss surgery in adolescents to determine whether SAD predicts MetS risk in this population. SETTING: Data were collected in the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study at 5 sites (U.S. children's hospitals) performing weight-loss surgery in adolescents. The current study is a secondary analysis of these data. METHODS: We examined data collected presurgery through 5 years postsurgery. MetS risk/severity was defined using the MetS severity z score (MetS-z), and MetS prevalence was determined using age-appropriate criteria. Association between SAD and MetS-z was evaluated with an adjusted linear mixed model. RESULTS: Among 228 individuals (75% female, 72% White), mean age 16.5 years and body mass index (BMI) 53 kg/m2, 79% met MetS criteria pre-urgery. MetS-z (1.5) and SAD (32cm) were correlated (r = 0.6, P < .0001) presurgery, and both improved significantly at 6 months, 1, and 5 years postsurgery, remaining highly correlated at each timepoint. SAD predicted MetS-z (ß = 0.118; 95% CI, 0.109, 0.127) after adjustment for age, visit, surgery type, and caregiver education. CONCLUSIONS: Abdominal obesity is a key MetS risk marker in youth undergoing weight loss surgery. Both SAD and Met-z measures may be useful for MetS risk assessment and tracking postsurgery changes in this population, but more research is needed to identify effective lifestyle interventions targeting abdominal obesity.


Subject(s)
Bariatric Surgery , Metabolic Syndrome , Child , Adolescent , Humans , Female , Male , Metabolic Syndrome/complications , Metabolic Syndrome/epidemiology , Sagittal Abdominal Diameter , Obesity, Abdominal/complications , Obesity/epidemiology , Body Mass Index , Bariatric Surgery/adverse effects , Risk Factors
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